6tbc
From Proteopedia
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<StructureSection load='6tbc' size='340' side='right'caption='[[6tbc]], [[Resolution|resolution]] 2.55Å' scene=''> | <StructureSection load='6tbc' size='340' side='right'caption='[[6tbc]], [[Resolution|resolution]] 2.55Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6tbc]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TBC OCA]. For a <b>guided tour on the structure components</b> use [http:// | + | <table><tr><td colspan='2'>[[6tbc]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TBC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TBC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=N5H:(2~{E},5~{R},10~{E},12~{E},15~{S},19~{R})-20-[[(2~{R},3~{R})-3-aminocarbonyloxy-2-methyl-butanoyl]amino]-3,5,15-trimethyl-7-methylidene-19-oxidanyl-17-oxidanylidene-icosa-2,10,12-trienoic+acid'>N5H</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N5H:(2~{E},5~{R},10~{E},12~{E},15~{S},19~{R})-20-[[(2~{R},3~{R})-3-aminocarbonyloxy-2-methyl-butanoyl]amino]-3,5,15-trimethyl-7-methylidene-19-oxidanyl-17-oxidanylidene-icosa-2,10,12-trienoic+acid'>N5H</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> |
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADPH,_Re-specific) Enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.39 1.3.1.39] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADPH,_Re-specific) Enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.39 1.3.1.39] </span></td></tr> | ||
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6tbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tbc OCA], [http://pdbe.org/6tbc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tbc RCSB], [http://www.ebi.ac.uk/pdbsum/6tbc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tbc ProSAT]</span></td></tr> |
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The enoyl-acyl carrier protein reductase enzyme FabI is essential for fatty acid biosynthesis in Staphylococcus aureus and represents a promising target for the development of novel, urgently needed anti-staphylococcal agents. Here, we elucidate the mode of action of the kalimantacin antibiotics, a novel class of FabI inhibitors with clinically-relevant activity against multidrug-resistant S. aureus . By combining X-ray crystallography with molecular dynamics simulations, in vitro kinetic studies and chemical derivatization experiments, we characterize the interaction between the antibiotics and their target, and we demonstrate that the kalimantacins bind in a unique conformation that differs significantly from the binding mode of other known FabI inhibitors. We also investigate mechanisms of acquired resistance in S. aureus and identify key residues in FabI that stabilize the binding of the antibiotics. Our findings provide intriguing insights into the mode of action of a novel class of FabI inhibitors that will inspire future anti-staphylococcal drug development. | ||
| + | |||
| + | The kalimantacin polyketide antibiotics inhibit fatty acid biosynthesis in Staphylococcus aureus by targeting the enoyl-acyl carrier protein binding site of FabI.,Fage CD, Lathouwers T, Vanmeert M, Gao LJ, Vrancken K, Lammens EM, Weir A, Degroote R, Cuppens H, Kosol S, Simpson TJ, Crump MP, Willis CL, Herdewijn P, Lescrinier E, Lavigne R, Anne J, Masschelein J Angew Chem Int Ed Engl. 2020 Mar 24. doi: 10.1002/anie.201915407. PMID:32208550<ref>PMID:32208550</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6tbc" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 07:25, 8 April 2020
Crystal structure of S. aureus FabI in complex with NADPH and kalimantacin B
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